The present invention relates to anticancer and anti-obesity agents based on cyclic peptide compounds. More particularly, the agents are derivatives of cycloheptapeptides. It is a goal of the present invention to provide cyclopeptide compounds having anticancer and anti-obesity activity.
More than 10 million people are diagnosed with cancer every year in the world. Cancer has become a leading cause of death. According to the compiled statistics by WHO, cancer claimed the lives of more than 8.2 million people worldwide in 2012 (WHO: http://www.who.int/mediacentre/factsheets/fs297/en/index.html; retrieved on 18 Sep. 2016). Although numerous cancer chemotherapeutics are available today, they often have very narrow therapeutic indices and very severe side effects. In addition, cancers can and often do develop resistance to many of these drugs. The fact that there currently are no drugs available that are capable of curing cancer diseases, the discovery and development of new anticancer drugs are very much needed and the undertaking of such studies is imperative.
Obesity, the metabolic disease, has become increasingly concerned in modern society. It affects nearly a third population of adults in the developed countries, and more than 1.9 billion adults were overweight in 2014 according to WHO report (http://www.who.int/mediacentre/factsheets/fs311/en/, retrieved on 18 Sep. 2016). Many health problems such as cardiovascular diseases, type 2 diabetes, cancer and osteoarthritis are associated with obesity. Obesity is largely preventable, and in fact, it is considered to be a leading preventable cause of death in the world. However, the number of people with obesity in the world is more than doubled since 1980. Obesity, the once considered a wealthy country problem is now on the rise in low- and middle-income countries. Therefore, in many cases, treatment may become inevitable option. There are only a few anti-obesity drugs (orlistat, lorcaserin hydrochloride and Qsymia™) approved by the FDA for long term use. The drugs have side effects associated with high blood pressure, rapid heart eat, palpitations, drug addiction, hallucination, constipation and insomnia. To develop new anti-obesity drugs is thus needed.
Cyclopeptides (cyclic peptide) are peptide compounds whose amino and carboxyl termini are linked together by a peptide bond to form a circular chain. Cyclodepsipeptides have at least one lactone linkage in place of one of the amides. A cycloheptapeptide is the cyclopeptide compound containing seven amino acid residues.
A large number of cyclopeptides have been synthesized due to their variety of biological activities including anticancer activity (White C J, Yudin A K. Contemporary strategies for peptide macrocylization. Nature Chemistry 2011; 3: 509-524. Chatterjee J, Gilon C, Hoffman A, Kessler H. N-methylation of peptides: a new perspective in medicinal chemistry. Accounts of Chemical Research 2008; 41: 1331-1342). However, cyclopeptides containing rare amino acids are seldom reported either from synthetic study or from nature. The inventor has discovered novel cyclopeptides that contain a unique amino acid residue in the structure.
Citation or identification of any reference in this section or any other section of this application shall not be construed as an admission that such reference is available as prior art for the present application.